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1.
Can J Ophthalmol ; 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38428829

RESUMO

OBJECTIVE: Females in ophthalmology represent a small proportion of senior positions. Participation in academic endeavours (e.g., involvement at conferences) plays a crucial role in promoting a physician's career. This study evaluates the representation of females from 2003 to 2021 at the Canadian Ophthalmology Society (COS) annual meeting. DESIGN: Retrospective cross-sectional study. METHODS: Data were extracted for the following and classified according to gender (female or male): oral presentations, free workshops, skills transfer courses, committee members, moderators, keynote speakers, and panelists. Percentages of gender were calculated and trended per category and in aggregate. RESULTS: The total percentage of females in any conference position demonstrated a positive trend. Over 18 years, there was an 18.2% increase in females (24.9%-43.1%). Excluding duplicates, only a 12.7% increase (27.4%-40.1%) was found. An increase in representation among all categories was observed, most significantly in female committee members (14.3%-50.0%). Female keynote speakers continue to be the most underrepresented category (8.33%-35.0%). CONCLUSIONS: While underrepresented, females continue to trend upward in participation at COS meetings. Continuous analysis of females participating in academic positions such as at COS meetings will aid in limiting gender disparities in ophthalmology.

2.
Mol Omics ; 19(9): 697-705, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37540205

RESUMO

Globally, obesity is a severe health issue. A more precise and practical approach is required to enhance clinical care and drug development. The FTO (fat mass and obesity-associated) gene variant rs1421085 is strongly associated with an increased susceptibility to obesity in numerous populations; however, the precise mechanism behind this association concerning metabolomics is still not understood. This study aims to examine the association between metabolites and obesity-related anthropometric traits based on the variant FTO rs1421085. This study was based on a case-control design involving a total of 542 participants including overweight/obese cases and healthy controls. The blood samples were collected from all the participants. The isolated serum samples were subjected to untargeted metabolomics using GC-MS. The isolated DNA samples were genotyped for the FTO rs1421085 variant. Initially, a total of 42 metabolites were identified on GC-MS, which were subjected to further association analyses. The study observed a significant association of two metabolites, glycerol and 2,3-dihydroxypropyl stearate with FTO gene variant rs1421085 and obesity-related anthropometric traits including % BF, WHtR, WC, and HC. The CT genotype of FTO rs1421085 may greatly increase the risk of overweight/obesity by changing the lipid metabolism-related metabolites. Therefore, this study highlights the significance of biochemical networks in the progression of obesity in carriers of the FTO rs1421085 risk genotype.


Assuntos
Metabolismo dos Lipídeos , Sobrepeso , Humanos , Sobrepeso/genética , Metabolismo dos Lipídeos/genética , Polimorfismo de Nucleotídeo Único , Obesidade/genética , Genótipo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética
3.
J Infect Dev Ctries ; 15(9): 1351-1355, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34669607

RESUMO

INTRODUCTION: District Sheikhupura encountered its first dengue outbreak in 2014 but lacked serological evidence and reports of risk factors associated with it. To assess this, a hospital-based study was conducted from January 2014 to December 2017. METHODOLOGY: Blood from 333 participants was collected, the serum obtained was tested for IgG and IgM antibodies against DENV using a commercially available ELISA kit. RESULTS: The results showed that out of all (n= 333) samples tested, 120 were turned up positive for DENV, making an overall prevalence of 36%. Of the 120 confirmed cases, 55% (n = 66) were recorded in 2014, 10% (n = 12) in 2015, 27.5% (n = 33) in 2016, and 7.5% (n = 9) in 2017. It was found that 68.3% (n = 82) were male and 31.7% (n = 38) were female, with 61% (n = 74) patients aged between 11-30 years. The highest prevalence of infection, 94.2% (n = 113), was noted after the rainy season. During the study, the highest number of cases appeared in Ferozewala Tehsil. The factors age, gender, and season were found statistically significant with the prevalence of infection (p < 0.05). CONCLUSIONS: The study is the first report on the detection of dengue in the Sheikhupura district. The survey anticipated its geographical expansion, determined associated risk factors, and suggests active disease surveillance in the area.


Assuntos
Vírus da Dengue/isolamento & purificação , Dengue/epidemiologia , Surtos de Doenças , Adolescente , Adulto , Criança , Estudos Transversais , Dengue/sangue , Dengue/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Fatores de Risco , Estudos Soroepidemiológicos , Inquéritos e Questionários , Adulto Jovem
4.
Mol Genet Genomics ; 296(4): 919-938, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33966103

RESUMO

The studies investigating gene-gene and gene-environment (or gene-behavior) interactions provide valuable insight into the pathomechanisms underlying obese phenotypes. The Pakistani population due to its unique characteristics offers numerous advantages for conducting such studies. In this view, the current study was undertaken to examine the effects of gene-gene and gene-environment/behavior interactions on the risk of obesity in a sample of Pakistani population. A total of 578 adult participants including 290 overweight/obese cases and 288 normal-weight controls were involved. The five key obesity-associated genetic variants namely MC4R rs17782313, BDNF rs6265, FTO rs1421085, TMEM18 rs7561317, and NEGR1 rs2815752 were genotyped using the TaqMan allelic discrimination assays. The data related to behavioral factors, such as eating pattern, diet consciousness, the tendency toward fat-dense food (TFDF), sleep duration, sleep-wake cycle (SWC), shift work (SW), and physical activity levels were collected via a questionnaire. Gene-gene and gene-behavior interactions were analyzed by multifactor dimensionality reduction and linear regression, respectively. In our study, only TMEM18 rs7561317 was found to be significantly associated with anthropometric traits with no significant effect of gene-gene interactions were observed on obesity-related phenotypes. However, the genetic variants were found to interact with the behavioral factors to significantly influence various obesity-related anthropometric traits including BMI, waist circumference, hip circumference, waist-to-hip ratio, waist-to-height ratio, and percentage of body fat. In conclusion, the interaction between genetic architecture and behavior/environment determines the outcome of obesity-related anthropometric phenotypes. Thus, gene-environment/behavior interaction studies should be promoted to explore the risk of complex and multifactorial disorders, such as obesity.


Assuntos
Interação Gene-Ambiente , Comportamentos Relacionados com a Saúde , Obesidade , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Índice de Massa Corporal , Peso Corporal/genética , Estudos de Casos e Controles , Comportamento Alimentar/fisiologia , Preferências Alimentares/fisiologia , Estudos de Associação Genética , Predisposição Genética para Doença , Comportamentos Relacionados com a Saúde/fisiologia , Estilo de Vida , Obesidade/epidemiologia , Obesidade/etiologia , Obesidade/genética , Sobrepeso/epidemiologia , Sobrepeso/etiologia , Sobrepeso/genética , Paquistão/epidemiologia , Polimorfismo de Nucleotídeo Único , Fatores de Risco
5.
Sci Rep ; 11(1): 8320, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33859285

RESUMO

Obesity is an outcome of multiple factors including environmental and genetic influences. Common obesity is a polygenic trait indicating that multiple genetic variants act synergistically to influence its expression. We constructed a genetic risk score (GRS) based on five genetic variants (MC4R rs17782313, BDNF rs6265, FTO rs1421085, TMEM18 rs7561317, and NEGR1 rs2815752) and examined its association with obesity-related traits in a sample of Pakistanis. The study involved 306 overweight/obese (OW/OB) and 300 normal-weight (NW) individuals. The age range of the study participants was 12-63 years. All anthropometric and metabolic parameters were measured for each participant via standard procedures and biochemical assays, respectively. The genetic variants were genotyped by allelic discrimination assays. The age- and gender-adjusted associations between the GRS and obesity-related anthropometric and metabolic measures were determined using linear regression analyses. The results showed that OW/OB individuals had significantly higher mean ranks of GRS than NW individuals. Moreover, a significant association of the GRS with obesity-related anthropometric traits was seen. However, the GRS did not appear to affect any obesity-related metabolic parameter. In conclusion, our findings indicate the combined effect of multiple genetic variants on the obesity-related anthropometric phenotypes in Pakistanis.


Assuntos
Pesos e Medidas Corporais , Estudos de Associação Genética , Variação Genética/genética , Herança Multifatorial/genética , Obesidade/genética , Obesidade/metabolismo , Adolescente , Adulto , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Moléculas de Adesão Celular Neuronais/genética , Criança , Proteínas Ligadas por GPI/genética , Humanos , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Obesidade/patologia , Paquistão , Fenótipo , Receptor Tipo 4 de Melanocortina/genética , Fatores de Risco , Adulto Jovem
6.
Data Brief ; 35: 106813, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33604430

RESUMO

This data article describes the dataset of the International COVID-19 Impact on Parental Engagement Study (ICIPES). ICIPES is a collaborative effort of more than 20 institutions to investigate the ways in which, parents and caregivers built capacity engaged with children's learning during the period of social distancing arising from global COVID-19 pandemic. A series of data were collected using an online survey conducted in 23 countries and had a total sample of 4,658 parents/caregivers. The description of the data contained in this article is divided into two main parts. The first part is a descriptive analysis of all the items included in the survey and was performed using tables and figures. The second part refers to the construction of scales. Three scales were constructed and included in the dataset: 'parental acceptance and confidence in the use of technology', 'parental engagement in children's learning' and 'socioeconomic status'. The scales were created using Confirmatory Factor Analysis (CFA) and Multi-Group Confirmatory Analysis (MG-CFA) and were adopted to evaluate their cross-cultural comparability (i.e., measurement invariance) across countries and within sub-groups. This dataset will be relevant for researchers in different fields, particularly for those interested in international comparative education.

7.
Alcohol Clin Exp Res ; 44(5): 1046-1060, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32267550

RESUMO

BACKGROUND: Excess alcohol (ethanol, EtOH) consumption is a significant cause of chronic liver disease, accounting for nearly half of the cirrhosis-associated deaths in the United States. EtOH-induced liver toxicity is linked to EtOH metabolism and its associated increase in proinflammatory cytokines, oxidative stress, and the subsequent activation of Kupffer cells. Dihydromyricetin (DHM), a bioflavonoid isolated from Hovenia dulcis, can reduce EtOH intoxication and potentially protect against chemical-induced liver injuries. But there remains a paucity of information regarding the effects of DHM on EtOH metabolism and liver protection. As such, the current study tests the hypothesis that DHM supplementation enhances EtOH metabolism and reduces EtOH-mediated lipid dysregulation, thus promoting hepatocellular health. METHODS: The hepatoprotective effect of DHM (5 and 10 mg/kg; intraperitoneal injection) was evaluated using male C57BL/6J mice and a forced drinking ad libitum EtOH feeding model and HepG2/VL-17A hepatoblastoma cell models. EtOH-mediated lipid accumulation and DHM effects against lipid deposits were determined via H&E stains, triglyceride measurements, and intracellular lipid dyes. Protein expression of phosphorylated/total proteins and serum and hepatic cytokines was determined via Western blot and protein array. Total NAD+ /NADH Assay of liver homogenates was used to detect NAD + levels. RESULTS: DHM reduced liver steatosis, liver triglycerides, and liver injury markers in mice chronically fed EtOH. DHM treatment resulted in increased activation of AMPK and downstream targets, carnitine palmitoyltransferase (CPT)-1a, and acetyl CoA carboxylase (ACC)-1. DHM induced expression of EtOH-metabolizing enzymes and reduced EtOH and acetaldehyde concentrations, effects that may be partly explained by changes in NAD+ . Furthermore, DHM reduced the expression of proinflammatory cytokines and chemokines in sera and cell models. CONCLUSION: In total, these findings support the utility of DHM as a dietary supplement to reduce EtOH-induced liver injury via changes in lipid metabolism, enhancement of EtOH metabolism, and suppressing inflammation responses to promote liver health.


Assuntos
Etanol/efeitos adversos , Etanol/metabolismo , Flavonóis/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatopatias Alcoólicas/prevenção & controle , Fígado/metabolismo , Adenilato Quinase/metabolismo , Animais , Suplementos Nutricionais , Ativação Enzimática/efeitos dos fármacos , Fígado Gorduroso Alcoólico/prevenção & controle , Células Hep G2 , Humanos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Triglicerídeos/metabolismo
8.
Eat Weight Disord ; 25(5): 1321-1332, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31468339

RESUMO

PURPOSE: Genetic variants determine the predisposition of an individual to obesity in a given environment. The present study was conducted to seek an association of the FTO variant rs1421085 with overweight/obesity and related traits in 612 Pakistani subjects in a case-control manner (overweight/obese = 306 and non-obese = 306). Moreover, interaction effects of the rs1421085 and overweight/obesity on multiple metabolic traits were also investigated, which were never explored before in Pakistani as well as in any other population. MATERIALS AND METHODS: Anthropometric traits were measured by standard procedures, while metabolic parameters were determined by biochemical assays. Genotyping of the rs1421085 was carried out by TaqMan allelic discrimination assay. The data were analysed using SPSS software version 19. RESULTS: The study revealed a significant association of the rs1421085 with overweight/obese phenotype with respect to over-dominant model indicated by h-index. The CT genotype of the rs1421085 was observed to increase the risk of being overweight/obese by 1.583 times (95% CI 1.147-2.185, p = 0.005). The CT genotype was also found to be associated with higher values of all anthropometric variables (except height and waist-to-hip ratio). Moreover, the interaction between the CT genotype of the rs1421085 and overweight/obesity was found to influence several metabolic parameters (raised blood pressure, product of triglyceride and glucose index, triglyceride levels, LDL-C, VLDL-C, coronary risk index, atherogenic index, and triglyceride-to-HDL-C ratio). CONCLUSION: In conclusion, the rs1421085 was found to be associated with overweight/obesity and related anthropometric traits independent of age and gender in Pakistani population. Moreover, this variant was found to influence various metabolic traits in the presence of overweight/obesity. LEVEL OF EVIDENCE: Level III, case-control analytic study.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato , Obesidade , Sobrepeso , Polimorfismo de Nucleotídeo Único , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Índice de Massa Corporal , Predisposição Genética para Doença , Genótipo , Humanos , Obesidade/genética , Sobrepeso/genética , Paquistão
9.
J Biosci ; 44(4)2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31502573

RESUMO

The current case-control study sought the association of BDNF rs6265 and MC4R rs17782313 with metabolic syndrome (MetS), MetS components and other related metabolic parameters in a sample of Pakistani subjects. Fasting high-density lipoprotein cholesterol (HDL-C) and homeostatic model assessment of insulin sensitivity showed a significantly lower mean whereas body mass index (BMI), waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose, insulin, total cholesterol (TC), low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, triglycerides (TG), cholesterol to HDL-C ratio, TG to HDL-C ratio, homeostatic model assessment of insulin resistance, visceral adiposity index, lipid accumulation product and the product of TG and glucose showed a significantly higher mean in the presence of MetS. Reduced HDL-C appeared as the most frequent and hypertriglyceridemia as the least frequent component of MetS whereas clustering of reduced HDL-C + abdominal obesity (AO) + hyperglycemia appeared as the most prevalent combination of MetS components. Moreover, BDNF rs6265 showed BMI and gender independent association with increased risk of MetS in Pakistani individuals whereas MC4R rs17782313 showed BMI and gender dependent association with increased risk of MetS in Pakistani females. In addition, BDNF rs6265 and MC4R rs17782313 showed gender-dependent associations with decreased risk of having low HDL-C in males and increased risk of having abdominal obesity in females, respectively. However, no association was observed for metabolic variables other than components of MetS across genotypes of both BDNF rs6265 and MC4R rs17782313.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Estudos de Associação Genética , Síndrome Metabólica/genética , Receptor Tipo 4 de Melanocortina/genética , Adulto , Idoso , Glicemia , Índice de Massa Corporal , HDL-Colesterol/sangue , HDL-Colesterol/genética , LDL-Colesterol/sangue , LDL-Colesterol/genética , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Insulina/sangue , Insulina/genética , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Obesidade Abdominal , Paquistão/epidemiologia , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Triglicerídeos/sangue , Triglicerídeos/genética
10.
Can J Ophthalmol ; 53(5): 474-479, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30340714

RESUMO

OBJECTIVE: To use the perspectives of undergraduate program directors to assess the current structure and adequacy of undergraduate ophthalmology curricula at Canadian medical schools. DESIGN: Cross-sectional survey. PARTICIPANTS: Undergraduate ophthalmology program directors at each English-speaking Canadian medical school. METHODS: Program directors were identified and invited to participate in an online survey. The 18-question survey focused on key areas of undergraduate ophthalmology curricula, including length, timeline, setting, and nature of medical students' exposure to ophthalmology. A period of 4 months was allowed for responses. Information from medical school web sites was combined with survey responses. RESULTS: Responses were obtained from 7 of the 14 (50%) program directors. All of the respondents represented metropolitan institutions of greater than 100 seats. After combining survey and web site data, only 5 of 14 (35.7%) schools were found to have a mandatory clinical clerkship ophthalmology rotation. In each case, the mandatory rotation is less than 2 weeks. A core curriculum based on the International Council of Ophthalmology (ICO) guidelines is used in only 20% of schools. Extracurricular ophthalmology exposure in the form of research opportunities and interest groups exists in 100% and 71.4% of schools, respectively. CONCLUSIONS: The proportion of schools requiring mandatory clerkship ophthalmology rotations is only 35.7%. However, most departments use strategies to optimize the limited time allotted to ophthalmology rotations during medical school. A greater degree of adherence to the ICO curriculum guidelines may help to ensure that medical students develop an appropriate level of proficiency in managing patients with eye disease.


Assuntos
Competência Clínica , Currículo , Educação de Graduação em Medicina/organização & administração , Oftalmologia/educação , Faculdades de Medicina/organização & administração , Canadá , Estudos Transversais , Humanos
11.
J Med Entomol ; 55(4): 1011-1015, 2018 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-29462424

RESUMO

Aedes aegypti (L.) and Aedes albopictus (Skuse) are known vectors of dengue, chikungunya, and other pathogens; however, their ecology and role in virus transmission has not been well studied in Pakistan. Here, we report on an intensive survey of potential breeding sites of Ae. aegypti in Rawalpindi, Punjab Province, Pakistan. The study continued for 11 mo and was divided into three seasons: January to June (pre-monsoon), July to September (monsoon), and October-November (post-monsoon). Larval mosquitoes were collected from all wet containers present in and around the houses. Altogether 5,570,418, 2,930,508, and 1,507,111 water-filled containers were examined during each season, of which 2,703, 8,843, and 3,439 were found positive for Ae. aegypti larvae or pupae, yielding Breteau indices of 0.46, 2.92, and 1.99%, respectively. Among 14 container types examined, the breeding preference ratio during all seasons was highest for roof-top water tanks and room evaporative coolers, followed by discarded tires and urban trash. The study concluded that increased urbanization, insufficient water supply and inefficient removal of urban trash resulted in increased numbers of nonbiodegradable containers around human dwellings, thereby creating ideal breeding habitats for Ae. aegypti. Measures such as integrated vector management, minimization of the breeding potential of Ae. aegypti by water management, proper disposal of discarded tires and urban trash, and health education were recommended for control of Ae. aegypti.


Assuntos
Aedes/fisiologia , Mosquitos Vetores/fisiologia , Aedes/crescimento & desenvolvimento , Distribuição Animal , Animais , Dengue , Larva/crescimento & desenvolvimento , Larva/fisiologia , Mosquitos Vetores/crescimento & desenvolvimento , Oviposição , Paquistão , Dinâmica Populacional , Pupa/crescimento & desenvolvimento , Pupa/fisiologia , Estações do Ano
12.
J Vector Borne Dis ; 53(2): 136-43, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27353583

RESUMO

BACKGROUND & OBJECTIVES: Dengue is one of the most common arthropod-borne viral diseases which is transmitted mainly by two vector species, Aedes aegypti (Linnaeus 1762) and Ae. albopictus (Skuse, 1894) worldwide. As there is no effective medicine and vaccine available, vector control remains the most effective measure to prevent its transmission and outbreak. The aim of the study was to confirm the co-occurrence of Aedes aegypti and Ae. albopictus populations in the different localities of Rawalpindi, Pakistan and examine their susceptibility status against different groups of insecticides. METHODS: Ovitraps were randomly placed in the study localities. The number of eggs from all the ovitraps were counted and incubated for hatching in Medical Entomology and Disease Vector Control (MEDVC) insectarium for rearing up to adult stage. The adults were then identified by using the pictorial keys. Spatial distribution and aggregation of both Ae. aegypti and Ae. albopictus populations was determined by using Index of dispersion or variance to mean ratio and k values of the negative binomial distribution. The susceptibility status of both the species against different insecticides was assessed by using the World Health Organization (WHO) standard bioassay tests. RESULTS: The results showed that there was coexistence among Ae. aegypti and Ae. albopictus populations and the aggregation of their eggs was also observed in all the localities studied in Rawalpindi. Larval bioassays of both the populations exhibited incipient resistance against temephos while adult susceptibility testing results showed that both the species were resistant to DDT, malathion, bendiocarb and permethrin. INTERPRETATION & CONCLUSION: The results suggested that all the field populations of Ae. aegypti and Ae. albopictus existed together and showed qualitative changes in their susceptibility status. Resistance against deltamethrin and lambdacyhalothrin was not confirmed and further investigation was recommended to confirm the change in their susceptibility status. This study could help public health authorities to apply simultaneous control activities on both species due to their coexistence and also resistance management strategies should be formulated to slow down the process of development of resistance.


Assuntos
Aedes/efeitos dos fármacos , Aedes/crescimento & desenvolvimento , Dengue/epidemiologia , Inseticidas/farmacologia , Filogeografia , Animais , Bioensaio , Feminino , Humanos , Resistência a Inseticidas , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Masculino , Paquistão/epidemiologia
14.
Clin Physiol Funct Imaging ; 31(6): 415-21, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21981451

RESUMO

We studied the relative importance of the magnitude and duration of the shear stimulus to induce flow-mediated dilation (FMD) in the brachial artery of 10 healthy men by ultrasound imaging. The shear stress stimulus was induced by different durations of reactive hyperaemia following 15-min forearm occlusion. The control condition of continuous postocclusion hyperaemia was compared to 20, 40 and 60 s of reactive hyperaemia followed by reapplication of circulatory arrest for 2 min and a second cuff release. In response to the first cuff release, peak shear rate was not different between conditions; total shear during the first minute was reduced in the 40 s and further reduced in the 20 s conditions. FMD in control (10·0 ± 3·0%), 60 s (10·5 ± 3·2%) and 40 s (7·8 ± 3·6%) were greater than the 20-s condition (2·9 ± 2·8%). At second cuff release, peak shear of the 20-s condition was slightly reduced from the first release, but 40 and 60-s conditions were progressively reduced. Total shear to peak dilation was reduced after the second cuff release for the 20 and 40-s conditions and further after the 60-s condition. FMD was maintained in the 20-s condition (8·3 ± 3·7%) but reduced in the 40-s (3·7 ± 1·7%) and 60-s conditions (1·5 ± 2·6%). FMD was not related to peak shear rate after the first occlusion (r = 0·003) but was after the second cuff release (r = 0·32, P = 0·004). The FMD response was correlated with the total shear to time of peak diameter after the first (r = 0·35, P<0·001) and the second (r = 0·25, P = 0·009) cuff release.


Assuntos
Artéria Braquial/fisiopatologia , Hiperemia/fisiopatologia , Vasodilatação , Artéria Braquial/diagnóstico por imagem , Constrição , Humanos , Hiperemia/diagnóstico por imagem , Análise dos Mínimos Quadrados , Masculino , Variações Dependentes do Observador , Ontário , Valor Preditivo dos Testes , Fluxo Sanguíneo Regional , Reprodutibilidade dos Testes , Estresse Mecânico , Fatores de Tempo , Ultrassonografia Doppler de Pulso
15.
Circ Res ; 103(6): 643-53, 2008 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-18688045

RESUMO

Ischemic preconditioning (IPC) is a potent cellular protective mechanism whereby brief periods of sublethal ischemia protect the myocardium from prolonged ischemia-induced injury. We demonstrate the selective role of phosphatidylinositol 3-kinase (PI3K) isoforms in IPC. Hearts from PI3Kgamma knockout mice (PI3Kgamma(-/-)) displayed poorer functional recovery and greater tissue injury following IPC compared to wild-type and PI3Kgamma(+/-) hearts. Examination of the cell-signaling pathways revealed restored phosphorylation levels of Akt and glycogen synthase kinase (GSK)3beta in wild-type hearts, which were abolished in PI3Kgamma(-/-) hearts subjected to IPC. Inhibition of GSK3beta by LiCl reversed the loss in protection in PI3Kgamma(-/-) hearts. In contrast, mice expressing a cardiac-specific kinase-deleted PI3Kalpha (PI3KalphaDN) were resistant to injury induced by 30 minutes of ischemia followed by 40 minutes of reperfusion. Furthermore, the resistance of PI3KalphaDN hearts to ischemia/reperfusion correlated with the persistent expression of p110gamma and was blocked by the PI3K inhibitor wortmannin, suggesting the possible enhanced cell signaling through the PI3Kgamma pathway. These results demonstrate the importance of the PI3Kgamma-Akt-GSK3beta signaling pathway in IPC. Selective activation of myocardial PI3Kgamma may be an attractive target for the treatment of ischemic heart disease.


Assuntos
Adenosina/farmacologia , Precondicionamento Isquêmico Miocárdico/métodos , Isquemia Miocárdica/enzimologia , Isquemia Miocárdica/prevenção & controle , Fosfatidilinositol 3-Quinases/fisiologia , Adenosina/uso terapêutico , Animais , Classe Ib de Fosfatidilinositol 3-Quinase , Isoenzimas/deficiência , Isoenzimas/genética , Isoenzimas/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Isquemia Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/enzimologia , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Fosfatidilinositol 3-Quinases/deficiência , Fosfatidilinositol 3-Quinases/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
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